The long-term goal of this research project is to develop more effective oral vaccines against Vibrio cholerae, the causative agent of cholera, a life threatening diarrheal disease that remains endemic in many parts of the developing world. While there is mounting evidence from epidemiological studies to suggest that IgA antibodies directed against bacterial lipopolysaccharide (LPS) are the primary determinants of immunity to V. cholerae, virtually nothing is known about how these antibodies affect the bacterium's capacity to colonize the intestinal epithelium. This proposal will test the hypothesis that the binding of LPS-specific IgA (and IgG) antibodies to the surface of V. cholerae has direct impact on bacterial physiology and virulence. Aim 1 will test the hypothesis that LPS-specific IgA (and IgG) antibodies induce changes in V. cholerae membrane potential, permeability and ultrastructure. Aim 2 will test the hypothesis that LPS-specific IgA (and IgG) antibodies also trigger changes in the bacterial virulence gene expression and signal transduction pathways. The principal investigator is a leading expert in the field of IgA-pathogen interactions, while key personnel have expertise in V. cholerae physiology and virulence.